Abstract: Objective To investigate the clinical efficacy and safety of long-term application of entecavir for patients with lamivudine-resistant chronic hepatitis B. Methods 98 patients with lamivudine resistant chronic hepatitis B in our hospital between January 2007 and January 2009 were recruited and were treated with entecavir at dose of 1 mg daily. The application of adefovir dipivoxil combination with lamivudine were given in 27 patients because of virological rebound. The clinical efficacy,virologic rebound rate,HBV DNA negative rate,HBsAg and HBeAg nageive rate,ALT normalization and adverse reactions were observed. Results At the end of 24 weeks of treatment,the total response rate was 88.8%,as the prolongation of treatment,the total response gradually increased,and at the end of 192 weeks of treatment,the total response rate reached to 92.9%;there was no virologic rebound at 24 weeks,there was 6 cases with virologic rebound at 48 weeks of treatment,and the virological rebound rate increased gradually with the prolongation of treatment and at the end of the 8-year observation,the virological rebound rate was up to 27.6%;serum HBV DNA negative rate were up to 46.9% at 96 weeks after treatment,serum HBV DNA negative rate increased slowly and it reached to 60.2% at the end of the observation;there was no serum HBeAg or HBsAg turn to negative before 48 weeks of treatment,and there were 31 cases with serum HBeAg negativity and 12 got serum HBsAg negative at the end of the observation; serum ALT levels decreased with the prolonged treatment,and at the end of 12 weeks of treatment,serum ALT levels gradually returned to normal;there were 25 cases （25.5%） with adverse reactions including 8 cases with fatigue,6 cases with tachycardia,10 cases with nausea and 1 cases with a white blood cell detection in urine. Conclusion Long-term application of entecavir in the treatment of patients with lamivudine-resistant chronic hepatitis B has significant clinical efficacy with no obvious adverse reaction,which warrants further investigation.

Key words: Hepatitis B, Entecavir, Lamivudine-resistant, Rescued therapy